Method for producing organic alkyne compounds

ABSTRACT

The invention relates to a method for producing organic alkyne compounds of formula (I), X—C═C—Y According to said method, organic halogen compounds of formula (Ia), X-Hal, are reacted with organic terminal alkyne compounds of formula (Ib), H—C═C—Y, X and Y representing the same or different organic radicals and Hal representing chlorine or bromine, in inert solvents under the action of microwave radiation, in the presence of at least one metallic compound and at least one base.

The present invention relates to a process for preparing organic alkynecompounds of the formula IX—C≡C—Y   (I)by reacting organic halogen compounds of the formula IaX-Hal   (Ia),with organic terminal alkyne compounds of the formula IbH—C≡C—Y   (Ib),where X and Y are identical or different organic radicals and Hal ischlorine or bromine, in inert solvents under the action of microwaveenergy, in the presence of at least one metal compound and at least onebase.

Under the customary conditions of the Sonogashira reaction, aryl oralkenyl halides are reacted with terminal alkyne compounds underpalladium and copper salt catalysis at elevated temperature to givecorrespondingly substituted alkyne compounds.

A distinct reduction in the reaction time can be achieved by carryingout the reaction under the action of microwave radiation.

For instance, J.-X. Wang et al. (J. Chem. Research (S), 2000, p.536-537) describe reactions of different terminal alkynes with organiciodine compounds in the presence of copper(I) iodide/triphenylphosphineand potassium carbonate in dimethylformamide (DMF). The comparison ofthe reactions show in table 2 of this publication, on the one hand underreflux of DMF, and on the other hand under the action of a microwaveradiation source having an output of 375 W shows impressively that whencomparable yields are obtained, the reactions in the latter case proceedmore quickly than in the former case by factors of from 48 to 144.

Investigations of solvent-free reactions of aryl, heteroaryl and vinyliodides with terminal alkynes in the presence of palladium/copper(I)iodide/triphenylphosphine and potassium fluoride supported on aluminumoxide under the action of microwave radiation have been carried out byG. W. Kabalka et al. (Tetrahedron Lett. 41, 2000, p. 5151-5154). Theauthors mention (p. 5152) that aryl chlorides and bromides did not reactand that the starting materials were recovered unchanged.

We have now been found that, surprisingly, organic chlorine and brominecompounds can be reacted with terminal organic alkyne compounds to givealkyne derivatives in good to very good yields.

Accordingly, a process has been found for preparing organic alkynecompounds of the formula IX—C≡C—Y   (I)by reacting organic halogen compounds of the formula IaX-Hal   (Ia),with organic terminal alkyne compounds of the formula IbH—C≡C—Y   (Ib),where X and Y are identical or different organic radicals in inertsolvents under the action of microwave energy, in the presence of atleast one metal compound and at least one base, wherein Hal is chlorineor bromine.

In this context, inert solvents are liquids or liquid mixtures whichunder the reaction conditions react neither with the reactants nor withthe products.

In particular, such inert solvents are polar, aprotic liquids, since theuse of protic liquids may lead to undesired secondary reactions whichare triggered off by protonation.

To simplify the discussion, the terms “solvent” and “dissolve” willhereinbelow be used, even when in individual cases, for example, thebase or bases or metal compound or metal compounds used are notcompletely dissolved, but are instead in suspension (or emulsion).

Preference is given to using those metal compounds which comprise ametal selected from the group consisting of magnesium, calcium,strontium, barium, titanium, zirconium, hafnium, iron, ruthenium,osmium, cobalt, rhodium, iridium, nickel, palladium, platinum, copper,silver, gold, zinc, cadmium and mercury. Particular preference is givento using copper compounds.

Emphasis is given to the metal halide compounds, in particular thechlorides and bromides, but also the iodides, of the metals mentioned.When these halides form adducts with triarylphosphines, for exampletriphenylphosphine, they are advantageously used in the form of theseadducts.

Metal compounds further include the metals themselves, in particular theabovementioned metals in elemental form. Furthermore, combinations ofmore than one metal compound, more than one metal, and also combinationsof metals and metal compounds may be used. The metal species which iscatalytically active in the reaction does not necessarily have to beidentical to the metal compounds added, but can instead only be formedin situ by reaction with the reactants and/or the base or bases.

The organic radicals X and Y are saturated or unsaturated hydrocarbonradicals, and also hydrocarbon radicals which contain both saturated andunsaturated moieties. The hydrocarbon radicals may further containcustomary heteroatoms, such as nitrogen, oxygen, phosphorus, sulfur,fluorine, chlorine, bromine or iodine. The organic radicals X and Ycustomarily have molar masses of up to about 600 g/mol. However, inindividual cases, the molar masses of the X and Y radicals may also behigher.

Preferred organic radicals X and Y contain saturated or unsaturatedcarbo- or heterocyclic radicals where both -Hal, i.e. chlorine orbromine, and H—C≡C— are bonded directly to the saturated or unsaturatedcarbo- or heterocyclic radicals.

In particular, X is a radical of the formula IIaP¹—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-   (IIa)andY is a radical of the formula IIb-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²—P²   (IIb)where

-   -   P¹ and P² are each independently hydrogen, C₁-C₂-alkyl, a        polymerizable group, a group suitable for polymerization or a        radical which carries a polymerizable group or a group suitable        for polymerization,    -   or    -   P¹ and/or P² each corresponds to a radical P^(1′) and/or P^(2′)        which denotes a precursor group which is stable under the        reaction conditions which can be reacted to give the        corresponding polymerizable group or group suitable for        polymerization P¹ and/or P² or the radicals P¹ and/or P² which        carry a polymerizable group or a group suitable for        polymerization,    -   Y¹, Y^(2,) Y³ and Y⁴ are each independently a single chemical        bond, —O—, —S—, —CO—, —CO—O—, —O—CO—, —CO—N(R)—, —(R)N—CO—,        —O—CO—O—, —O—CO—N(R)—, —(R)N—CO—O— or —(R)N—CO—N(R)—,    -   B¹ and B² are each independently a single chemical bond, —C≡C—,        —O—, —S—, —CO—, —CO—O—, —O—CO—, —CO—N(R)—, —(R)N—CO—, —O—CO—O—,        —O—CO—N(R)—, —(R)N—CO—O— or —(R)N—CO—N(R)—,    -   each R is, independently and irrespective of the meaning in each        of Y¹ to Y⁴, B¹ and B², hydrogen or C₁-C₄-alkyl,    -   A¹ and A² are each independently spacers having from 1 to 30        carbon atoms,    -   T¹, T², T³ and T⁴ are each independently bivalent, saturated or        unsaturated, carbo- or heterocyclic radicals and    -   m′, m, n′ and n are each independently 0 or 1.

The T¹ to T⁴ radicals in the formulae IIa and IIb are in particularthose selected from the group consisting of

Useful C₁-C₁₂-alkyl radicals for P¹ and P² in formula I include branchedand unbranched C₁-C₁₂-alkyl chains, for example methyl, ethyl, n-propyl,1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl,1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl,3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl,1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl,3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl,1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl,3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl,1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl,n-heptyl, n-octyl, 2-ethylhexyl, n-nonyl, n-decyl, n-undecyl andn-dodecyl.

Preferred P¹ and P² alkyl radicals are the branched and unbranchedC₁-C₆-alkyl chains, such as methyl, ethyl, n-propyl, 1-methylethyl,n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, n-pentyl,1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl,1-ethylpropyl and n-hexyl.

Useful polymerizable groups or groups which are suitable forpolymerization or radicals which carry a polymerizable group or a groupsuitable for polymerization (such groups or radicals are referred tohereinbelow simply as “reactive radicals”) for P¹ and P² are inparticular:

where the R¹ to R³ radicals can be identical or different and are eachhydrogen or C₁-C₄-alkyl, such as methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl or tert-butyl.

Useful polymerizable groups for P¹ and P² are in particular theacrylate, methacrylate and vinyl radicals.

Useful C₁-C₄-alkyl radicals in the —CO—N(R)—, —(R)N—CO—, —O—CO—N(R)—,—(R)N—CO—O— and —(R)N—CO—N(R)— groups listed under the bridging units Y¹to Y⁴, B¹ and B² include methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, sec-butyl and tert-butyl. When one or two R radicals arepresent in the Y¹ to Y⁴, B¹ and B² units, any R radicals present in theremaining units may be identical or different. The same applies to thecase where there are two R radicals in one unit.

Useful spacers A¹ and A² include all groups known to those skilled inthe art for this purpose. The spacers generally have from one to 30,preferably from one to 12, more preferably from one to six, carbon atomsand consist of predominantly linear aliphatic groups. They may beinterrupted in the chain by, for example, nonneighboring oxygen orsulfur atoms or imino or alkylimino groups, for example methyliminogroups. Useful substituents for the spacer chain include fluorine,chlorine, bromine, cyano, methyl and ethyl.

Examples of representative spacers include:

where u, v and w are integers and u is from 1 to 30, preferably from 1to 12, v is from 1 to 14, preferably from 1 to 5, and w is from 1 to 9,preferably from 1 to 3.

Preferred spacers are ethylene, propylene, n-butylene, n-pentylene andn-hexylene.

The T¹ to T⁴ radicals are ring systems which may be substituted byfluorine, chlorine, bromine, cyano, hydroxyl, formyl, nitro, C₁-C₂₀-alkyl, C₁ -C₂₀-alkoxy, C₁-C₂₀-alkoxycarbonyl, C₁-C₂₀-monoalkylaminocarbonyl, C₁-C₂₀-alkylcarbonyl,C₁-C₂₀-alkylcarbonyloxy or C₁-C₂₀-alkylcarbonylamino.

Preferred T¹ to T⁴ radicals are:

When the reactive P¹ and/or P² radicals are unstable under the reactionconditions, the reactantsP¹′—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-Hal and/orH—C≡C-T⁴-(B²-T²-)_(n)(Y⁴-A²)_(n′)-Y²—P^(2′)may be used as starting materials where the P¹′ and/or P²′ radicals areprecursor groups which are stable under the reaction conditions and areconverted to or substituted by the corresponding reactive P¹ and/or P²radicals in a subsequent step.

Compounds which, for example, have the constructionP¹′—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²—P^(2′)may be regarded as direct products of the preparative process accordingto the invention.

Owing to retrosynthetic considerations, it may also be sensible toprepare the alkyne compounds by the process according to the inventionwhich correspond to the fragments-(A¹-Y³)_(m′)-(T¹B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²—P²,-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)(Y⁴-A²)_(n′)-Y²—P^(2′),-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²—P²,-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²—P^(2′),P¹—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-,P¹′—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-,P¹—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-,P¹′—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-,-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-,-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-,-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)- or-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-and then convert these in one or more subsequent steps using theappropriate complementary compounds to the target compoundsP¹—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²-P²′

Examples of compounds to which the above-listed fragments correspondincludeHO-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²—P²,HO-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²—P^(2′),HO-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²—P²,HO-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²—P^(2′),P¹—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴A²)_(n′)-OH,P¹′—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-OH,P¹—Y¹-(A¹-Y³)_(m′)-(T¹-B¹)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-OH,P¹′—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-OH,HO-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-Y⁴-A²)_(n′)-OH,HO-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-OH,HO-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-OH orHO-(T¹-B¹-)_(m)-T³-C≡C-T⁴-(B²-T²-)_(n)-OH.

According to the definition of the X and Y radicals in the formulae IIaand IIb, the variables in the compounds listed are, in the same order inwhich they were listed, as follows:P¹=hydrogen, Y¹═—O—,P¹=hydrogen, Y¹═O—,P¹=hydrogen, Y¹═—O—, m′=0.P¹=hydrogen, Y¹═—O—, m′=0.P²=hydrogen, Y²═—O—,P²=hydrogen, Y²═—O—,P²=hydrogen, Y²═—O—,n′=0,P²=hydrogen, Y²═—O—,n′=0,P¹═P²=hydrogen, Y¹═Y²═—O—,P¹═P²=hydrogen, Y¹═Y²═—O—, n′=0,P¹═P²=hydrogen, Y¹═Y²═—O—, m′=0 andP¹═P²=hydrogen, Y¹═Y²═—O—, m′=n′=0.

Further, the hydroxyl group may be replaced by, for example, a carboxylgroup (P¹=hydrogen and Y¹═—OCO— and/or P²=hydrogen and Y²═—COO—). In thedifunctional compounds, both hydroxyl and carboxyl groups may also bepresent.

These hydroxyl or carboxylic acid or hydroxyl/carboxylic acid compoundswhich are given by way of example are again to be regarded as directproducts of the preparative process according to the invention.

The reactants of the formulae Ia and Ib are customarily dissolved in amolar ratio of from 2:1 to 1:2 together with the at least one metalcompound and the at least one base in the inert solvent. The solution isnormally prepared at room temperature, but in individual cases, may alsobe prepared at higher or lower temperatures.

The temperature during the actual reaction under the action of microwaveradiation is not critical. Customarily, the reaction is carried out attemperatures from room temperature to the boiling temperature of thesolvent used.

Preference is given to using dimethylformamide (“DMF”),N-methylpyrrolidone (“NMP”) or a mixture of the two as solvent.Particular preference is given to using DMF as solvent (or as suspendingmedium) in the process according to the invention.

Preference is given to selecting the at least one base from the groupconsisting of alkali metal carbonates, alkali metal phosphates andtri(C₁-C₄-alkyl)amines, and emphasis is given to the alkali metalcarbonates.

The group of suitable bases includes in particular sodium carbonate,potassium carbonate, sodium phosphate and potassium phosphate,trimethyl-, triethyl- and triisopropylamine.

Particular preference is given to using potassium carbonate.

In individual cases, the addition of potassium iodide may also beadvantageous for the reaction. Whether there is such a positive effectand how much potassium iodide should optionally be added can be easilydetermined by preliminary experiments.

The output of the microwave radiation source is customarily from ten tohundreds of watts and should be selected according to the volume of thereaction batch. The correct power of the radiation source is customarilyknown to those skilled in the art and/or can be easily determined bypreliminary experiments.

The alkyne compounds obtained are worked up and purified by customaryorganic synthesis methods.

EXAMPLES

The Experiments Described Hereinbelow Use the Following: SubstanceSource Purity 4-Chlorobenzoic acid Acros >99% 4-Bromobenzoic acidMerck >99% 4-Iodobenzoic acid EMKA-Chemie >99% PhenylacetyleneAldrich >98% Copper(I) iodide Merck >99% Triphenylphosphine Merck >99%Potassium carbonate Merck >99.9%   (ground) Dimethylformamide BASF >99%(“DMF”) Potassium iodide J. T. Baker >99%Experimental Procedure:General Reaction Equation:

5 mmol of 4-halobenzoic acid (halo: chloro, bromo or iodo), 7.5 mmol ofphenylacetylene, 0.5 mmol of copper(I) iodide, 1.0 mmol oftriphenylphosphine, 7.5 mmol of potassium carbonate and 10 ml of DMFwere initially charged under an argon atmosphere into a 100 ml four-neckflask provided with a magnetic stirrer, heated within 5 min to atemperature of 155° C. and subjected at reflux for 20 min to the maximumradiation output of a microwave device (MLS-Ethos 1600; unpulsed;magnetron frequency 2450 MHz; maximum output 375 W).

The workup was carried out by filtering off the solid (substantially inpotassium carbonate), washing with 100 ml of dichloromethane andextracting the solution obtained three times with 50 ml each time of asaturated, aqueous sodium chloride solution. The dichloromethanesolution was dried over sodium sulfate and then the solvent was removedon a rotary evaporator.

For comparative purposes, experiments were also carried out with theaddition of 0.5 mmol of potassium iodide. The amounts of the remainingsubstances used were unchanged; the experimental procedure and workupwere likewise identical to those described above.

Results:

The experimental results are reported in the following table. Potassium4-Halobenzoic Yield iodide acid Example (% of theory) addition Halo = 133.0 − I (Comparative) 2 74.4 − Cl 3 56.5 + Cl 4 54.5 − Br 5 38.6 + Br

When 4-iodobenzoic acid was used (example 1 (comparative), the lowestyields by far were obtained, but when 4-bromo- and in particular4-chlorobenzoic acid were used (examples 4 and 5, and 2 and 3respectively), distinctly higher yields of the desired target compoundwere obtained. In the experiments carried out here, the addition ofpotassium iodide (examples 3 and 5) caused a deterioration compared tothe potassium iodide-free experimental procedure (examples 2 and 4).However, it is conceivable that, in individual cases, the addition ofpotassium iodide may have an advantageous effect.

1. A process for preparing organic alkyne compounds of the formula IX—C≡—C—Y   (I) by reacting organic halogen compounds of the formula IaX-Hal   (Ia), with organic terminal alkyne compounds of the formula IbH—C≡—C—Y   (Ib), where X and Y are identical or different organicradicals in inert solvents under the action of microwave energy, in thepresence of at least one metal compound and at least one base, whereinHal is chlorine or bromine.
 2. A process as claimed in claim 1 which iscarried out in the presence of at least one metal compound selected fromthe group consisting of magnesium, calcium, strontium, barium, titanium,zirconium, hafnium, iron, ruthenium, osmium, cobalt, rhodium, iridium,nickel, palladium, platinum, copper, silver, gold, zinc, cadmium., amercury and mixtures thereof.
 3. A process as claimed in claim 1 whichis carried out in the presence of a copper compound.
 4. A process asclaimed in claim 1, wherein X and Y are identical or different and areeach organic radicals which contain saturated or unsaturated carbo- orheterocyclic radicals where both -Hal and H—C≡C— are bonded directly tosaid saturated or unsaturated carbo- or heterocyclic radicals.
 5. Aprocess as claimed in claim 1, wherein X is a radical of the formula IaP¹—Y¹-(A¹-Y³)_(m′)-(T¹-B¹-)_(m)-T³-   (IIa) and Y is a radical of theformula IIb-T⁴-(B²-T²-)_(n)-(Y⁴-A²)_(n′)-Y²—P²   (IIb) where P¹ and P² are eachindependently hydrogen, C₁-C₂-alkyl, a polymerizable group, a groupsuitable for polymerization or a radical which carries a polymerizablegroup or a group suitable for polymerization, or P¹ and/or P² eachcorresponds to a radical P^(1′) and/or P^(2′) which denotes a precursorgroup which is stable under the reaction conditions which can be reactedto give or be substituted by the corresponding polymerizable group orgroup suitable for polymerization P¹ and/or P² or the radicals P^(1′)and/or P^(2′) which carry a polymerizable group or a group suitable forpolymerization, Y¹, Y², Y³ and Y⁴ are each independently a singlechemical bond, —O—, —S—, —CO—, —CO—O—, —O—CO—, —CO—N(R)—, —(R)N—CO—,—O—CO—O—, —O—CO—N(R)—, —(R)NCO—O— or —(R)N—CO—N(R)—, B¹ and B² are eachindependently a single chemical bond, —C≡C—, —O—, —S—, —CO—, —CO—O—,—O—CO—, —CO—N(R)—, —(R)N—CO—, —O—CO—O—, —O—CO—N(R)—, —(R)N—CO—O— or—(R)—CO—N(R)—, each R is, independently and irrespective of the meaningin each of Y¹ to Y⁴, B¹ and B², hydrogen or C₁-C₄-alkyl, A¹ and A² areeach independently spacers having from 1 to 30 carbon atoms, T¹, T², T³and T⁴ are each independently bivalent, saturated or unsaturated, carboor heterocyclic radicals and m′, m, n′ and n are each independently 0or
 1. 6. A process as claimed in claim 5, wherein the T¹ to T⁴ radicalsin the formulae IIa and IIb are selected from the group consisting of

and mixtures thereof.
 7. A process as claimed in claim 1, wherein theinert solvent used is dimethylformaniide or N-methyl-pyrrolidone or amixture of the two.
 8. A process as claimed in claim 1, wherein theinert solvent used is dimethylformamide.
 9. A process as claimed inclaim 1, wherein the at least one base is a compound selected from thegroup consisting of alkali metal carbonates, alkali metal phosphates,tri(C1-C4-alkyl)amines and mixtures thereof.
 10. A process as claimed inclaim 1, wherein the base used is at least one alkali metal carbonate.11. A process as claimed in claim 1, wherein the base used is potassiumcarbonate.